TTBK1

Summary

TTBK1 (tau tubulin kinase 1, HGNC:19140) is a protein-coding gene on chromosome 6p21.1, encoding Tau-tubulin kinase 1 (Q5TCY1). Serine/threonine kinase which is able to phosphorylate TAU on serine, threonine and tyrosine residues.

Summary:This gene belongs to the casein kinase 1 superfamily. The encoded protein is a neuron-specific, serine/threonine and tyrosine kinase, which regulates phosphorylation of tau, a protein that associates with microtubule assemblies and stabilizes them. Genetic variants in this gene are associated with Alzheimer’s disease.

Source: NCBI Gene 84630 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 251 total — 2 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_032538

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19140
Approved symbol	TTBK1
Name	tau tubulin kinase 1
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1855
Ensembl gene	ENSG00000146216
Ensembl biotype	protein_coding
OMIM	619415
Entrez	84630

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000259750, ENST00000304139, ENST00000703836

RefSeq mRNA: 1 — MANE Select: NM_032538 NM_032538

CCDS: CCDS34455

Canonical transcript exons

ENST00000259750 — 15 exons

Exon	Start	End
ENSE00000974509	43253568	43253708
ENSE00000974510	43254547	43254651
ENSE00000974511	43255049	43255114
ENSE00000974513	43255731	43255856
ENSE00000974514	43257812	43257966
ENSE00001034363	43284983	43288258
ENSE00001034370	43282727	43284312
ENSE00001034388	43259531	43259706
ENSE00001173105	43262789	43263350
ENSE00001173108	43259038	43259269
ENSE00001173113	43253291	43253364
ENSE00001745867	43255552	43255644
ENSE00001951188	43243481	43243708
ENSE00002704217	43246607	43246768
ENSE00003524145	43252739	43252886

Expression profiles

Bgee: expression breadth ubiquitous, 126 present calls, max score 86.47.

FANTOM5 (CAGE): breadth broad, TPM avg 2.6114 / max 108.5483, expressed in 232 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67892	2.5772	231
67891	0.0342	21

Top tissues by expression

228 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	86.47	gold quality
prefrontal cortex	UBERON:0000451	86.29	gold quality
postcentral gyrus	UBERON:0002581	85.83	gold quality
left ventricle myocardium	UBERON:0006566	85.50	gold quality
right frontal lobe	UBERON:0002810	85.39	gold quality
cardiac muscle of right atrium	UBERON:0003379	85.30	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.18	gold quality
frontal cortex	UBERON:0001870	84.98	gold quality
parietal lobe	UBERON:0001872	84.95	gold quality
cerebellar cortex	UBERON:0002129	84.77	gold quality
cerebellar hemisphere	UBERON:0002245	84.74	gold quality
superior frontal gyrus	UBERON:0002661	84.54	gold quality
cerebellum	UBERON:0002037	84.35	gold quality
neocortex	UBERON:0001950	84.28	gold quality
anterior cingulate cortex	UBERON:0009835	83.91	gold quality
cortical plate	UBERON:0005343	83.60	gold quality
entorhinal cortex	UBERON:0002728	83.48	gold quality
pancreatic ductal cell	CL:0002079	83.24	silver quality
kidney epithelium	UBERON:0004819	83.10	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.84	gold quality
cerebral cortex	UBERON:0000956	82.81	gold quality
temporal lobe	UBERON:0001871	82.43	gold quality
amygdala	UBERON:0001876	82.40	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.30	gold quality
nucleus accumbens	UBERON:0001882	82.16	gold quality
brain	UBERON:0000955	81.75	gold quality
forebrain	UBERON:0001890	81.71	gold quality
putamen	UBERON:0001874	81.62	gold quality
ventral tegmental area	UBERON:0002691	81.30	gold quality
pons	UBERON:0000988	81.28	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.27

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
CDK5R1	Activation
GRIN2B	Repression
GRIN2D	Repression

miRNA regulators (miRDB)

137 targeting TTBK1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4782-3P	99.88	73.31	735

Literature-anchored findings (GeneRIF, showing 11)

• TTBK1 in AD brain may be one of the underlying mechanisms inducing CDK5 and calpain activation, NR2B downregulation, and subsequent memory dysfunction. (PMID:19118186)
• This study demonistrated that TTBK1 is a promising new candidate tau phosphorylation-related gene for Alzheimer’s disease risk. (PMID:20096481)
• TTBK1 may play an important role in the pathogenesis of sporadic late-onset Alzheimer’s disease in a Han Chinese population. (PMID:21219968)
• The study suggested that a role for TTBK1 in pre-tangle formation prior to the formation of fibrillar tau and strengthen the idea that tau is phosphorylated at Ser422 at an early/intermediate stage in NFT formation. (PMID:23088643)
• X-ray diffraction data were collected and the structure of TTBK1 was determined by molecular replacement both as an apo structure and in complex with a kinase inhibitor (PMID:24637750)
• TTBK1/2 kinases may represent attractive targets for therapeutic intervention for TDP-43 proteinopathies such as Amyotrophic lateral sclerosis and Frontotemporal lobar degeneration-TDP. (PMID:25473830)
• Our findings suggest a possible etiology for the two most common frontotemporal lobar degeneration subtypes through a TTBK1/2 activation driven mechanism of neurodegeneration (PMID:29409526)
• miR-219-5p inhibits tau phosphorylation by targeting TTBK1 and GSK-3beta in Alzheimer’s disease. (PMID:30556160)
• Adult onset pan-neuronal human tau tubulin kinase 1 expression causes severe cerebellar neurodegeneration in mice. (PMID:33228809)
• The structural, functional, and dynamic effect of Tau tubulin kinase1 upon a mutation: A neuro-degenerative hotspot. (PMID:34297427)
• Modulation of tau tubulin kinases (TTBK1 and TTBK2) impacts ciliogenesis. (PMID:37059819)

Cross-species orthologs

67 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ttbk1	ENSMUSG00000015599
rattus_norvegicus	Ttbk1	ENSRNOG00000018416
drosophila_melanogaster	ball	FBGN0027889
drosophila_melanogaster	CG9962	FBGN0031441
caenorhabditis_elegans		WBGENE00007049
caenorhabditis_elegans		WBGENE00007269
caenorhabditis_elegans		WBGENE00007305
caenorhabditis_elegans		WBGENE00007335
caenorhabditis_elegans		WBGENE00007448
caenorhabditis_elegans		WBGENE00007777
caenorhabditis_elegans		WBGENE00007791
caenorhabditis_elegans		WBGENE00008088
caenorhabditis_elegans		WBGENE00008423
caenorhabditis_elegans		WBGENE00008464
caenorhabditis_elegans	F10G8.2	WBGENE00008662
caenorhabditis_elegans		WBGENE00008883
caenorhabditis_elegans		WBGENE00009324
caenorhabditis_elegans		WBGENE00009402
caenorhabditis_elegans		WBGENE00010555
caenorhabditis_elegans		WBGENE00010692
caenorhabditis_elegans		WBGENE00010874
caenorhabditis_elegans		WBGENE00011283
caenorhabditis_elegans		WBGENE00012169
caenorhabditis_elegans		WBGENE00012637
caenorhabditis_elegans		WBGENE00012731
caenorhabditis_elegans		WBGENE00013868
caenorhabditis_elegans		WBGENE00014007
caenorhabditis_elegans		WBGENE00015893
caenorhabditis_elegans		WBGENE00016111
caenorhabditis_elegans	C34B2.3	WBGENE00016388
caenorhabditis_elegans		WBGENE00016513
caenorhabditis_elegans		WBGENE00016541
caenorhabditis_elegans		WBGENE00016673
caenorhabditis_elegans		WBGENE00016765
caenorhabditis_elegans	C55B7.10	WBGENE00016946
caenorhabditis_elegans		WBGENE00016963
caenorhabditis_elegans		WBGENE00017050
caenorhabditis_elegans		WBGENE00017714
caenorhabditis_elegans		WBGENE00017725
caenorhabditis_elegans		WBGENE00017803
caenorhabditis_elegans		WBGENE00017895
caenorhabditis_elegans	F33D11.7	WBGENE00018004
caenorhabditis_elegans		WBGENE00018122
caenorhabditis_elegans		WBGENE00018123
caenorhabditis_elegans		WBGENE00018202
caenorhabditis_elegans		WBGENE00018203
caenorhabditis_elegans		WBGENE00018745
caenorhabditis_elegans		WBGENE00018839
caenorhabditis_elegans		WBGENE00019086
caenorhabditis_elegans		WBGENE00019119
caenorhabditis_elegans		WBGENE00019459
caenorhabditis_elegans		WBGENE00019556
caenorhabditis_elegans		WBGENE00019561
caenorhabditis_elegans		WBGENE00019562
caenorhabditis_elegans		WBGENE00019642
caenorhabditis_elegans	kin-35	WBGENE00019769
caenorhabditis_elegans		WBGENE00020071
caenorhabditis_elegans		WBGENE00020072
caenorhabditis_elegans		WBGENE00020223
caenorhabditis_elegans		WBGENE00020580
caenorhabditis_elegans	W09C3.1	WBGENE00021109
caenorhabditis_elegans	Y47G6A.13	WBGENE00021639
caenorhabditis_elegans	Y65B4A.9	WBGENE00022032
caenorhabditis_elegans		WBGENE00022102
caenorhabditis_elegans	Y71F9AL.2	WBGENE00022108
caenorhabditis_elegans		WBGENE00022705
caenorhabditis_elegans		WBGENE00022707

Paralogs (12): VRK2 (ENSG00000028116), CDC7 (ENSG00000097046), VRK1 (ENSG00000100749), VRK3 (ENSG00000105053), CSNK1A1 (ENSG00000113712), TTBK2 (ENSG00000128881), CSNK1G2 (ENSG00000133275), CSNK1D (ENSG00000141551), CSNK1G3 (ENSG00000151292), CSNK1G1 (ENSG00000169118), CSNK1A1L (ENSG00000180138), CSNK1E (ENSG00000213923)

Protein

Protein identifiers

Tau-tubulin kinase 1 — Q5TCY1 (reviewed: Q5TCY1)

Alternative names: Brain-derived tau kinase

All UniProt accessions (2): Q5TCY1, A0A994J709

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine kinase which is able to phosphorylate TAU on serine, threonine and tyrosine residues. Induces aggregation of TAU.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in the brain, particularly in cortical and hippocampal neurons. Weakly expressed in spinal cord and testis. No expression in adipose tissue, bladder, cervix, colon, esophagus, heart, kidney, liver, lung, ovary, placenta, prostate, skeletal muscle, small intestine, spleen, testis, thymus, thyroid or trachea.

Cofactor. Divalent metal cations. Mg(2+) or, to a lesser extent, Mn(2+), but not Ca(2+) or Zn(2+).

Similarity. Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5TCY1-1	1	yes
Q5TCY1-2	2

RefSeq proteins (1): NP_115927* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR042714	TTBK1_STKc	Domain
IPR050235	CK1_Ser-Thr_kinase-like	Family

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.11.26 — tau-protein kinase (BRENDA: 18 organisms, 200 substrates, 549 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (73 total): compositionally biased region 14, helix 13, strand 12, sequence variant 9, turn 6, region of interest 5, splice variant 3, sequence conflict 3, binding site 2, modified residue 2, chain 1, domain 1, active site 1, coiled-coil region 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
4NFN	X-RAY DIFFRACTION	1.42
7JXX	X-RAY DIFFRACTION	1.56
7ZHP	X-RAY DIFFRACTION	1.8
7ZHQ	X-RAY DIFFRACTION	1.8
7ZHN	X-RAY DIFFRACTION	1.85
4BTK	X-RAY DIFFRACTION	2
7Q8W	X-RAY DIFFRACTION	2.02
7ZHO	X-RAY DIFFRACTION	2.08
4NFM	X-RAY DIFFRACTION	2.12
7Q8V	X-RAY DIFFRACTION	2.13
7JXY	X-RAY DIFFRACTION	2.15
4BTJ	X-RAY DIFFRACTION	2.16
4BTM	X-RAY DIFFRACTION	2.54
8XPZ	X-RAY DIFFRACTION	2.6
7QHW	X-RAY DIFFRACTION	2.8
9HHW	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TCY1-F1	52.29	0.23

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 154 (proton acceptor)

Ligand- & substrate-binding residues (2): 40–48; 63

Post-translational modifications (2): 441, 540

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 136 (showing top): GGGACCA_MIR133A_MIR133B, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_POSITIVE_REGULATION_OF_MACROPHAGE_ACTIVATION, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_GLIAL_CELL_DIFFERENTIATION, GOBP_GLIAL_CELL_DEVELOPMENT, GOBP_REGULATION_OF_MACROPHAGE_ACTIVATION, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_ASTROCYTE_DIFFERENTIATION

GO Biological Process (9): signal transduction (GO:0007165), learning or memory (GO:0007611), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), substantia nigra development (GO:0021762), positive regulation of protein polymerization (GO:0032273), positive regulation of astrocyte activation (GO:0061890), positive regulation of microglial cell activation (GO:1903980), protein phosphorylation (GO:0006468)

GO Molecular Function (10): protein serine/threonine kinase activity (GO:0004674), protein tyrosine kinase activity (GO:0004713), ATP binding (GO:0005524), tau protein binding (GO:0048156), tau-protein kinase activity (GO:0050321), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), microtubule associated complex (GO:0005875), neuronal cell body (GO:0043025), perinuclear region of cytoplasm (GO:0048471), microtubule cytoskeleton (GO:0015630)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein kinase activity	3
gene expression	2
regulation of gene expression	2
positive regulation of neuroinflammatory response	2
cytoplasm	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
behavior	1
cognition	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
midbrain development	1
neural nucleus development	1
positive regulation of protein-containing complex assembly	1
regulation of protein polymerization	1
protein polymerization	1
astrocyte activation	1
positive regulation of astrocyte differentiation	1
positive regulation of cell activation	1
regulation of astrocyte activation	1
microglial cell activation	1
positive regulation of macrophage activation	1
regulation of microglial cell activation	1
phosphorylation	1
protein modification process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cytoskeletal protein binding	1
protein serine/threonine kinase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1

Protein interactions and networks

STRING

1744 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TTBK1	MAPT	P10636	506
TTBK1	DNAAF9	Q5TEA3	472
TTBK1	TARDBP	Q13148	445
TTBK1	CDK5	Q00535	440
TTBK1	SACK1E	Q2M2I3	390
TTBK1	GSK3B	P49841	381
TTBK1	KIF2A	O00139	365
TTBK1	CDC7	O00311	318
TTBK1	SACK1H	Q6ZRV2	315
TTBK1	PTPMT1	Q8WUK0	304
TTBK1	SACK1B	Q5T0W9	298
TTBK1	C12orf56	Q8IXR9	294
TTBK1	FAM222A	Q5U5X8	292
TTBK1	XKR8	Q9H6D3	289
TTBK1	STK32C	Q86UX6	288
TTBK1	VRK3	Q8IV63	288

IntAct

11 interactions, top by confidence:

A	B	Type	Score
TTBK1	YWHAG	psi-mi:“MI:0915”(physical association)	0.400
TTBK1	HNRNPC	psi-mi:“MI:0915”(physical association)	0.400
TTBK1	ACSL3	psi-mi:“MI:0915”(physical association)	0.400
DLST		psi-mi:“MI:0914”(association)	0.350
APP	ESYT2	psi-mi:“MI:0914”(association)	0.350
CUL4B	GGTLC3	psi-mi:“MI:0914”(association)	0.350
TTBK1	GABARAP	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
HEATR1	TTBK1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (29): TTBK1 (Co-fractionation), TTBK1 (Affinity Capture-MS), TTBK2 (Affinity Capture-MS), NUP205 (Affinity Capture-MS), GABARAPL2 (Affinity Capture-MS), HEATR1 (Affinity Capture-MS), TTBK1 (Biochemical Activity), MAPT (Biochemical Activity), TTBK1 (Affinity Capture-MS), TTBK1 (Affinity Capture-MS), TTBK1 (Proximity Label-MS), TTBK1 (Proximity Label-MS), TTBK1 (Proximity Label-MS), TTBK1 (Affinity Capture-MS), MAPRE1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I5ZN27, A6X8Z5, E1AZ71, F1N8V3, O35668, O54963, O70318, P20689, P48165, P51954, P54256, P54257, P55917, P62025, P70278, Q01538, Q13029, Q13127, Q14028, Q16799, Q28139, Q28181, Q2M1Z3, Q3SYS4, Q3UH66, Q4KMM3, Q4V8B0, Q5DW34, Q5IS59, Q5TCY1, Q62100, Q63HN8, Q640N3, Q64548, Q6IR42, Q6PCN3, Q7Z6I6, Q811Q2, Q8BYM7, Q8C5W0

Diamond homologs: A7E3X2, B9VVJ6, O15726, O19175, O74135, O76324, O80888, P16912, P22517, P23291, P23292, P28327, P29295, P34516, P34633, P35507, P35508, P35509, P39962, P40230, P40233, P40234, P40235, P40236, P42158, P42168, P48729, P48730, P49615, P49674, P51166, P54367, P67827, P67828, P67829, P67962, P67963, P78368, P81123, P97633

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
TTBK1	down-regulates	MAPT	phosphorylation
TTBK1	“up-regulates activity”	DPYSL2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

251 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	212
Likely benign	18
Benign	7

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
208398	NM_032538.3(TTBK1):c.773G>A (p.Arg258Gln)	Likely pathogenic
4073710	NM_032538.3(TTBK1):c.1899del (p.Thr634fs)	Likely pathogenic

SpliceAI

2687 predictions. Top by Δscore:

Variant	Effect	Δscore
6:43252737:A:AG	acceptor_gain	1.0000
6:43252738:G:GG	acceptor_gain	1.0000
6:43252876:G:GT	donor_gain	1.0000
6:43253562:A:AG	acceptor_gain	1.0000
6:43253563:T:G	acceptor_gain	1.0000
6:43253563:TGCA:T	acceptor_loss	1.0000
6:43253564:GCAG:G	acceptor_loss	1.0000
6:43253565:CA:C	acceptor_loss	1.0000
6:43253566:A:AG	acceptor_gain	1.0000
6:43253566:AG:A	acceptor_gain	1.0000
6:43253567:G:GT	acceptor_gain	1.0000
6:43253567:GG:G	acceptor_gain	1.0000
6:43253567:GGGCC:G	acceptor_gain	1.0000
6:43253704:AGCCT:A	donor_gain	1.0000
6:43253705:GCCT:G	donor_gain	1.0000
6:43253705:GCCTG:G	donor_gain	1.0000
6:43253706:CCT:C	donor_gain	1.0000
6:43253707:CT:C	donor_gain	1.0000
6:43253708:TG:T	donor_loss	1.0000
6:43253709:GTGA:G	donor_gain	1.0000
6:43253713:G:GG	donor_gain	1.0000
6:43254545:A:AG	acceptor_gain	1.0000
6:43254546:G:GG	acceptor_gain	1.0000
6:43254546:GTCA:G	acceptor_gain	1.0000
6:43254546:GTCAA:G	acceptor_gain	1.0000
6:43254647:GGCCC:G	donor_gain	1.0000
6:43254648:GCCC:G	donor_gain	1.0000
6:43254648:GCCCG:G	donor_gain	1.0000
6:43254652:G:GG	donor_gain	1.0000
6:43255043:CTGCA:C	acceptor_loss	1.0000

AlphaMissense

8472 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:43246749:T:A	V30D	1.000
6:43246758:G:C	R33P	1.000
6:43246760:T:A	W34R	1.000
6:43246760:T:C	W34R	1.000
6:43246761:G:C	W34S	1.000
6:43246762:G:C	W34C	1.000
6:43246762:G:T	W34C	1.000
6:43252752:G:A	G41E	1.000
6:43252763:T:A	F45I	1.000
6:43252763:T:C	F45L	1.000
6:43252764:T:C	F45S	1.000
6:43252764:T:G	F45C	1.000
6:43252765:T:A	F45L	1.000
6:43252765:T:G	F45L	1.000
6:43252766:G:C	G46R	1.000
6:43252767:G:A	G46D	1.000
6:43252773:T:G	I48S	1.000
6:43252775:T:G	Y49D	1.000
6:43252781:G:C	A51P	1.000
6:43252782:C:A	A51D	1.000
6:43252812:C:A	A61D	1.000
6:43252815:T:A	L62H	1.000
6:43252815:T:C	L62P	1.000
6:43252819:G:C	K63N	1.000
6:43252819:G:T	K63N	1.000
6:43252823:G:A	E65K	1.000
6:43252825:G:C	E65D	1.000
6:43252825:G:T	E65D	1.000
6:43252848:T:A	V73D	1.000
6:43252851:T:A	L74H	1.000

dbSNP variants (sampled 300 via entrez): RS1000054612 (6:43287905 C>A,G,T), RS1000060747 (6:43280570 C>G), RS1000086908 (6:43286383 A>G), RS1000106599 (6:43288168 C>A,G), RS1000148707 (6:43270206 G>A,T), RS1000186468 (6:43274463 T>C), RS1000258375 (6:43242516 C>G), RS1000282405 (6:43251011 G>C), RS1000285977 (6:43282051 C>A,T), RS1000288195 (6:43251397 C>A,G), RS1000387029 (6:43267516 A>T), RS1000520704 (6:43275790 C>T), RS1000591287 (6:43275489 G>C), RS1000597654 (6:43249461 A>T), RS1000630241 (6:43249726 G>A)

Disease associations

OMIM: gene MIM:619415 | disease phenotypes: MIM:209850, MIM:607834

GenCC curated gene-disease

Mondo (3): childhood-onset schizophrenia (MONDO:0957430), autism (MONDO:0005260), anxiety (MONDO:0011918)

Orphanet (1): Childhood-onset schizophrenia (Orphanet:641496)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST003272_2	Systolic blood pressure	2.000000e-16
GCST004521_164	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004775_24	Pulse pressure	7.000000e-07
GCST004776_25	Systolic blood pressure	3.000000e-06
GCST005978_10	Diastolic blood pressure	3.000000e-08
GCST005979_13	Systolic blood pressure	9.000000e-13
GCST006010_9	Mean arterial pressure	1.000000e-11
GCST006269_1180	General cognitive ability	3.000000e-08
GCST007329_26	Automobile speeding propensity	3.000000e-08
GCST008745_58	Estimated glomerular filtration rate in non-diabetics	2.000000e-08
GCST008899_1	Adult hearing difficulty	6.000000e-21
GCST010989_101	Body size at age 10	4.000000e-08
GCST012227_4	Hip circumference adjusted for BMI	2.000000e-09
GCST012227_5	Hip circumference adjusted for BMI	6.000000e-10
GCST90002384_93	Hemoglobin	2.000000e-13
GCST90002403_155	Red blood cell count	3.000000e-09

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0006336	diastolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0004337	intelligence
EFO:0008579	risk-taking behaviour
EFO:0009819	comparative body size at age 10, self-reported
EFO:0008039	BMI-adjusted hip circumference
EFO:0004509	hemoglobin measurement
EFO:0004305	erythrocyte count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001007	Anxiety	F01.470.132
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1926492 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Tau tubulin kinase (TTBK) family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
AMG28	Inhibition	6.7	pIC50

ChEMBL bioactivities

102 potent at pChembl≥5 of 108 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.80	IC50	1.6	nM	CHEMBL5182036
8.64	IC50	2.3	nM	CHEMBL5268795
8.64	IC50	2.3	nM	CHEMBL5283456
8.57	IC50	2.7	nM	CHEMBL5280210
8.57	IC50	2.7	nM	CHEMBL5193906
8.55	IC50	2.8	nM	CHEMBL5272364
8.11	IC50	7.8	nM	CHEMBL5279863
8.01	IC50	9.8	nM	CHEMBL5282072
8.00	IC50	10	nM	CHEMBL5268080
7.75	IC50	18	nM	CHEMBL5271137
7.75	IC50	18	nM	CHEMBL5273263
7.70	IC50	20	nM	CHEMBL5282902
7.50	IC50	32	nM	CHEMBL5290581
7.43	IC50	37	nM	CHEMBL5274162
7.41	IC50	39	nM	CHEMBL5280803
7.38	IC50	42	nM	CHEMBL5283456
7.24	IC50	57	nM	CHEMBL5288487
7.22	IC50	60	nM	CHEMBL5278744
7.07	IC50	86	nM	CHEMBL5274528
7.01	IC50	98	nM	CHEMBL5268795
6.94	IC50	114	nM	CHEMBL5282072
6.92	IC50	120	nM	CHEMBL4528881
6.92	IC50	120	nM	CHEMBL5193906
6.91	IC50	124	nM	CHEMBL5290252
6.79	IC50	164	nM	CHEMBL5279863
6.75	IC50	177	nM	CHEMBL5272364
6.73	IC50	185	nM	CHEMBL5279159
6.70	IC50	199	nM	CHEMBL2334586
6.65	IC50	224	nM	CHEMBL5282902
6.62	Kd	240	nM	CHEMBL127907
6.62	IC50	240	nM	CHEMBL5204869
6.62	IC50	239	nM	CHEMBL5268080
6.59	IC50	259	nM	CHEMBL5273263
6.50	IC50	315	nM	CHEMBL5280210
6.48	IC50	330	nM	CHEMBL5200069
6.47	IC50	340	nM	CHEMBL5193488
6.45	IC50	352	nM	CHEMBL5290252
6.45	IC50	352	nM	CHEMBL5275588
6.44	IC50	360	nM	CHEMBL5181249
6.43	IC50	370	nM	CHEMBL5184336
6.42	IC50	380	nM	CHEMBL5180098
6.42	IC50	377	nM	CHEMBL5275588
6.41	IC50	390	nM	CHEMBL5198544
6.41	IC50	390	nM	CHEMBL5178965
6.38	IC50	420	nM	CHEMBL5209196
6.38	IC50	414	nM	CHEMBL5272862
6.36	IC50	440	nM	CHEMBL5187459
6.35	IC50	450	nM	CHEMBL5187125
6.32	IC50	480	nM	CHEMBL5197012
6.28	IC50	520	nM	CHEMBL5185704

PubChem BioAssay actives

102 with measured affinity, of 192 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3R)-1-[1-(2-amino-6-methoxypyrimidin-4-yl)pyrrolo[3,2-c]pyridin-6-yl]-3-methylpent-1-yn-3-ol	1900241: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 30 mins by TR-FRET assay	ic50	0.0016	uM
4-[1-(2-aminopyrimidin-4-yl)-3-cyclopropylpyrrolo[3,2-c]pyridin-6-yl]-2-methylbut-3-yn-2-ol	1933471: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay	ic50	0.0023	uM
(3S)-1-[1-(2-aminopyrimidin-4-yl)pyrrolo[3,2-c]pyridin-6-yl]-3-methylpent-1-yn-3-ol	1933471: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay	ic50	0.0023	uM
3-[[5-[(4-amino-4-methylpiperidin-1-yl)methyl]pyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]-5-bromophenol	2124222: Inhibition of human recombinant catalytic domain TTBK1 (1 to 415 residues) extracted from Escherichia coli BL21 (DE3) incubated for 1 hr by spectrophotometric analysis	ic50	0.0027	uM
(3S)-1-[1-(2-amino-6-methoxypyrimidin-4-yl)pyrrolo[3,2-c]pyridin-6-yl]-3-methylpent-1-yn-3-ol	1933471: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay	ic50	0.0027	uM
4-[1-(2-aminopyrimidin-4-yl)-2,3-dihydropyrrolo[3,2-c]pyridin-6-yl]-2-methylbut-3-yn-2-ol	1933471: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay	ic50	0.0028	uM
4-[1-(2-aminopyrimidin-4-yl)-3-(oxan-4-yl)pyrrolo[3,2-c]pyridin-6-yl]-2-methylbut-3-yn-2-ol	1933471: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay	ic50	0.0078	uM
4-[1-(2-aminopyrimidin-4-yl)pyrrolo[3,2-c]pyridin-6-yl]-2-methylbut-3-yn-2-ol	1933471: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay	ic50	0.0098	uM
(3S)-1-[1-(2-amino-5-methoxypyrimidin-4-yl)pyrrolo[3,2-c]pyridin-6-yl]-3-methylpent-1-yn-3-ol	1933471: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay	ic50	0.0100	uM
(3S)-1-[1-(2-aminopyrimidin-4-yl)pyrazolo[4,5-c]pyridin-6-yl]-3-methylpent-1-yn-3-ol	1933471: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay	ic50	0.0180	uM
4-[1-(2-aminopyrimidin-4-yl)-3-[(3S)-1-methylpiperidin-3-yl]pyrrolo[3,2-c]pyridin-6-yl]-2-methylbut-3-yn-2-ol	1933471: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay	ic50	0.0180	uM
(3S)-1-[1-(2-amino-6-methylpyrimidin-4-yl)pyrrolo[3,2-c]pyridin-6-yl]-3-methylpent-1-yn-3-ol	1933471: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay	ic50	0.0200	uM
4-[1-(2-aminopyrimidin-4-yl)-4-morpholin-4-ylpyrrolo[3,2-c]pyridin-6-yl]-2-methylbut-3-yn-2-ol	1933471: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay	ic50	0.0320	uM
(3S)-1-[1-(6-aminopyrimidin-4-yl)pyrrolo[3,2-c]pyridin-6-yl]-3-methylpent-1-yn-3-ol	1933471: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay	ic50	0.0370	uM
4-[1-(2-aminopyrimidin-4-yl)-5-methoxyindol-6-yl]-2-methylbut-3-yn-2-ol	1933471: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay	ic50	0.0390	uM
4-[1-(2-aminopyrimidin-4-yl)-4-methoxypyrrolo[3,2-c]pyridin-6-yl]-2-methylbut-3-yn-2-ol	1933471: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay	ic50	0.0570	uM
4-[1-(2-aminopyrimidin-4-yl)pyrazolo[4,5-c]pyridin-6-yl]-2-methylbut-3-yn-2-ol	1933471: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay	ic50	0.0600	uM
4-[1-(2-aminopyrimidin-4-yl)-5-fluoroindol-6-yl]-2-methylbut-3-yn-2-ol	1933471: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay	ic50	0.0860	uM
3-[[5-[(4-amino-4-methylcyclohexyl)amino]pyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]-5-bromophenol	1529980: Inhibition of TTBK1 (unknown origin)	ic50	0.1200	uM
4-[3-(2-aminopyrimidin-4-yl)-1-methylindazol-5-yl]-2-methylbut-3-yn-2-ol	1933471: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay	ic50	0.1240	uM
4-[3-(2-aminopyrimidin-4-yl)-1H-indazol-5-yl]-2-methylbut-3-yn-2-ol	1933471: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay	ic50	0.1850	uM
4-(4-amino-3,5,12-triazatetracyclo[9.7.0.02,7.013,18]octadeca-1(11),2,4,6,13(18),14,16-heptaen-16-yl)-2-methylbut-3-yn-2-ol	1933471: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay	ic50	0.1990	uM
N-[4-(4-chlorophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.2400	uM
3-[(6,7-dimethoxyquinazolin-4-yl)amino]phenol	1529978: Binding affinity to phosphorylated TTBK1 (unknown origin) by SPR analysis	kd	0.2400	uM
N-[4-(2-chlorophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.3300	uM
N-[4-(4-methoxyphenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.3400	uM
4-[3-(2-aminopyrimidin-4-yl)-1-methylpyrazolo[5,4-c]pyridin-5-yl]-2-methylbut-3-yn-2-ol	1933471: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay	ic50	0.3520	uM
N-[4-[[1-[(2-chlorophenyl)methyl]triazol-4-yl]methoxy]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.3600	uM
4-N-[4-(3-chlorophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.3700	uM
4-N-[4-[4-(trifluoromethyl)phenoxy]phenyl]-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.3800	uM
N-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.3900	uM
N-[4-[[1-(2-phenylethyl)triazol-4-yl]methoxy]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.3900	uM
(E)-4-[1-(2-aminopyrimidin-4-yl)pyrrolo[3,2-c]pyridin-6-yl]-2-methylbut-3-en-2-ol	1933471: Inhibition of GST-tagged TTBK1 (1 to 421) (unknown origin) using DNA Topoisomerase 2-alpha-Thr1342 as substrate incubated for 15 mins followed by ATP addition and further incubated for 120 mins by TR-FRET assay	ic50	0.4140	uM
N-[4-(4-nitrophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.4200	uM
4-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)phenoxy]benzonitrile	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.4400	uM
4-N-[4-(4-chlorophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.4500	uM
N-[4-[[1-[(3-chlorophenyl)methyl]triazol-4-yl]methoxy]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.4800	uM
N-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.5200	uM
N-[4-(4-aminophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.5200	uM
N-[4-[[1-[(4-chlorophenyl)methyl]triazol-4-yl]methoxy]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.6100	uM
N-[4-(4-aminophenyl)sulfanylphenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.6500	uM
N-(4-phenylmethoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.7500	uM
N-[4-(4-bromophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.7500	uM
N-(4-pyridin-3-yloxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.7500	uM
N-[4-(4-fluorophenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.7700	uM
N-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.7900	uM
N-[4-(3-methoxyphenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.8400	uM
N-[4-[[1-[(4-methylphenyl)methyl]triazol-4-yl]methoxy]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	0.9900	uM
N-[4-(trifluoromethoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	1.0000	uM
N-[4-(4-methylphenoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1900242: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP	ic50	1.0200	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases methylation	2
bisphenol F	affects cotreatment, increases methylation	1
mivebresib	decreases expression	1
dicrotophos	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
benzo(e)pyrene	decreases methylation, increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation, increases methylation	1
Caffeine	affects phosphorylation	1
Clozapine	increases expression	1
Cuprizone	increases expression	1
Haloperidol	increases expression	1
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment	1
Methapyrilene	increases methylation, decreases methylation	1
Triclosan	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	affects methylation	1
Asbestos, Crocidolite	increases methylation	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

74 unique, capped per target: 74 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1930474	Binding	Inhibition of TTBK1 assessed as residual activity at 10 uM using [33P-ATP] by radiometric filter binding assay	Fragment based lead discovery of small molecule inhibitors for the EPHA4 receptor tyrosine kinase. — Eur J Med Chem

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms